Immunohistochemical comparison of uterine papillary serous and papillary endometrioid carcinoma: clues to pathogenesis.

Twenty-four predominantly papillary carcinomas of the endometrium, 10 serous and 14 endometrioid, were compared using a variety of immunohistochemical antibodies, including p53, estrogen and progesterone receptors, carcinoembryonic antigen, and E-cadherin. These were selected to attempt to find clues to explain the disparate behavior of these two tumor subtypes. We found that 6 of 8 (75%) serous carcinomas had a p53 reactivity score of 300, whereas 90% of endometrioid tumors had a p53 reactivity score of less than 20 (p = 0.0008). Combined estrogen and progesterone hormone reactivity was positive in 13 (100%) of endometrioid lesions compared with 4 of 8 (50%) of serous lesions (p = 0.0117). The significantly greater p53 expression and its significantly diminished hormone receptor expression indicate that papillary serous carcinomas belong to the type II group of endometrial carcinomas that occur in a background of atrophic endometrium, are high grade, present with high stage disease, and have a poor prognosis. In contrast, papillary endometrioid carcinomas, which belong to type I carcinomas, often arise in a background of estrogen-stimulated endometrial hyperplasia, are usually well-differentiated, and have a good prognosis. Early p53 mutations in papillary serous carcinoma as well as in endometrial intraepithelial serous carcinoma may partially explain their proclivity for early intra-abdominal dissemination. Carcinoembryonic antigen expression was similar in both groups and therefore is not useful to characterize possible differences in the cell of origin. The reactivity scores for E-cadherin were also similar in the two tumor subtypes, thus not supporting the hypothesis that decreased cell to cell adhesion molecules might contribute to early dissemination of serous lesions.     

Hysteroscopic and immunohistochemical findings in type I and type II endometrial carcinomas

STUDY OBJECTIVE: To determine whether types I and II endometrial carcinomas have different precursor lesions recognized at hysteroscopy and immunohistochemistry. DESIGN: Single center case study (Canadian Task Force classification II-2). SETTING: A private, university affiliated hospital. PATIENTS: One hundred forty-six postmenopausal women with endometrial pathology diagnosed by hysteroscopy and biopsy. INTERVENTION: Hysteroscopy and immunohistochemical determination of p53 overexpression. MEASUREMENTS AND MAIN RESULTS: The number of cells showing p53 overexpression was low in endometrial polyps, hyperplasia, and G1 endometrioid carcinomas. A marked increase was seen only in high-grade G2-G3 endometrioid carcinomas and in cases of uterine papillary serous carcinoma. In the latter, strong p53 overexpression was detected in early forms still confined to endometrial polyps. Hysteroscopy could not differentiate between high- and low-grade endometrioid carcinomas. CONCLUSION: The p53-driven pathway plays an important role in the origin of papillary serous carcinoma but not in G1 endometrioid cancer that evolves from estrogen-stimulated endometrium. However, this pathway is important for progression of low-grade endometrioid carcinomas to higher-grade tumors.     

Uterine papillary serous carcinoma: A study on 108 cases with emphasis on the prognostic significance of associated endometrioid carcinoma, absence of invasion, and concomitant ovarian carcinoma

One hundred eight cases of uterine papillary serous carcinoma (UPSC) were analyzed to characterize its histologic features and biologic behavior. Special situations that could conceivably modify the behavior and therapeutic approaches were considered: (1) the occurrence of areas of endometrioid carcinoma in otherwise typical UPSC; (2) the confinement of UPSC to an otherwise benign endometrial polyp or the endometrial mucosa or absence of residual tumor at the time of hysterectomy; and (3) the coexistence of a superficial UPSC and a serous ovarian carcinoma. There was coexistence of endometrioid and UPSC in 22 cases, and tumor was confined to an endometrial polyp or endometrium in 19 cases. There was simultaneous pathologic stage I UPSC and papillary serous ovarian carcinoma in 10 cases. In patients with pathologic stages I and II UPSC the presence of areas of endometrioid carcinoma intermixed with the UPSC did not improve survival. Patients with stage I disease and no residual tumor or tumor confined to an endometrial polyp/endometrial mucosa and without vascular invasion had a survival not statistically different from those with stage I disease but with myometrial and/or vascular invasion. Patients with stage I UPSC with concomitant ovarian serous surface papillary carcinoma had survival not statistically different from patients with stage IV UPSC.     

Uterine serous papillary carcinoma: Histopathologic changes within the female genital tract

Abstract. Jordan LB, Abdul-Kader M, Al-Nafussi A. Uterine serous papillary carcinoma: Histopathologic changes within the female genital tract.
The histopathologic features of 25 patients with uterine serous papillary carcinoma (USPC) were presented, with particular emphasis on the changes seen in the remaining müllerian epithelium. The mean age at presentation was 68.9 years; 52% of patients were stage III at the time of presentation and 40% died of their disease within 24 months of diagnosis. Histologic assessment revealed: 1) pure serous carcinoma in 56% of patients and mixed differentiation of serous and endometrioid in the remainder; 2) malignant epithelium reminiscent of that of USPC and akin to carcinoma in situ , frequently seen in the remaining endometrium, cervix, and, less commonly, the fallopian tube; 3) residual endometrium that, when identified (11/25 cases), was atrophic in all cases; 4) various types of cervical involvement in 17 cases (68%) ; 5) tumor within the fallopian tube in three cases (12%); and 6) carcinoma with in situ -like features in five cases (20%). In conclusion, it appears that USPC is frequently associated with malignant epithelial changes (as with carcinoma in situ ) in the remaining müllerian epithelium. This finding suggests either a field change or, more likely, a transepithelial tumor spread. The latter theory is preferable, because this type of spread is frequently seen on serosal surfaces in cases of serous ovarian carcinoma. Uterine serous papillary carcinoma is, therefore, biologically more akin to its ovarian counterpart.     

E-cadherin expression in endometrioid,papillary serous,and clear cell carcinoma of the endometrium

OBJECTIVE: To compare the frequency and pattern of E-cadherin expression in endometrioid, papillary serous, and clear cell carcinomas of the endometrium. METHODS: E-cadherin expression was examined in 76 endometrial carcinomas by immunohistochemistry using a monoclonal antibody to E-cadherin and was correlated with poor prognostic indicators such as depth of myometrial invasion, lymph node status, and intraperitoneal spread. The frequency of expression was compared between endometrioid, papillary serous, and clear cell carcinomas by the Fisher exact test. Logistic regression was used to examine the simultaneous effect of histological type and tumor grade on E-cadherin expression. RESULTS: Sixty-three endometrioid, nine papillary serous, two clear cell, and two carcinomas of mixed histology were examined. E-cadherin negative tumors were more likely to be poorly differentiated (P <.01), have cervical extension (P =.02), have positive peritoneal cytology (P <.01), and have adnexal spread (P =.01) when compared with E-cadherin positive tumors. Papillary serous and clear cell carcinomas were significantly less likely to express E-cadherin than endometrioid carcinoma (38% versus 95%, P <.001). Tumor grade and histological type were identified as significant predictors of E-cadherin expression in univariable analysis; however, only histological type remained significant in multivariable analysis (P =.01). When grade was controlled, endometrioid carcinoma remained 23 times more likely to express E-cadherin than papillary serous and clear cell carcinomas. CONCLUSION: Papillary serous and clear cell carcinomas are significantly less likely to express E-cadherin than endometrioid tumors. This difference may account for the more aggressive behavior of papillary serous and clear cell carcinomas.     

Malignant papillary lesions of the endometrium

In a review of 440 patients treated for endometrial adenocarcinoma at this center since 1974, 21 patients with tumors of papillary histology were identified. Eleven (2.5%) lesions contained histologic changes characteristic of uterine papillary serous carcinoma: complex papillary architecture, high nuclear/cytoplasmic ratio, and irregular epithelial tufting. Ten lesions (2.3%) containing areas of papillary morphology but lacking the criteria for the diagnosis of papillary serous tumors were termed papillary endometrioid adenocarcinoma. Patient age, stage, and the presence of obesity, hypertension, and diabetes were similar in both groups and reflected those characteristics well established for endometrial adenocarcinoma in general. Fewer papillary serous tumors (16.7%) and papillary endometrioid tumors (33.3%) contained progesterone receptors than did other adenocarcinomas (52.3%). In clinical stage I, surgical findings indicating a more advanced stage were present in 40% of patients with papillary serous tumors compared to 10% in papillary endometrioid tumors and 12.5% in nonpapillary adenocarcinomas (P = 0.03, Fisher's exact test). Recurrences were observed in 50% of patients with papillary serous lesions compared to 42.9% in papillary endometrioid lesions and 24.3% in other adenocarcinomas. Survival for clinical stage I papillary serous tumors was worse than that for nonpapillary grade 3 controls (P = 0.042) and survival for papillary endometrioid lesions was not different from that of the same controls. These findings support those of J. L. Chen, D. C. Trost, and E. J. Wilkinson (Int. J. Gynecol. Pathol. 4, 279-288 (1985)) that papillary serous and papillary endometrioid adenocarcinomas represent two distinct subtypes of papillary endometrial neoplasia.     

Comparative immunohistochemical study of endometrioid and serous papillary carcinoma of endometrium.

OBJECTIVE: The aim of this study was to determine whether immunohistochemical analysis of molecular parameters can provide an alternative method for classification of endometrial cancer cases according to their aggressiveness. METHODS: Sixty-four cases of endometrial carcinoma were assigned to three groups: group I--28 cases of endometrioid well and moderately differentiated (G1-G2) carcinoma; group II--14 cases of endometrioid poorly differentiated (G3) carcinoma; group III--22 cases of serous papillary endometrial cancer. Immunohistochemistry was used to determine the existence of estrogen receptors (ER), progesterone receptors (PR), and the expression of bcl-2, p53, HER-2/neu and Ki-67. RESULTS: There was a significant difference in the immunohistochemical profile of the studied molecular parameters comparing the three study groups. The endometrioid G1-G2 cases (group I) were characterized by increased immunoreactivity for ER and PR (85.7% and 78.6%, respectively), increased immunoreactivity for bcl-2 (42.8%) and low expression of p53 (14.3%) and HER-2/neu (14.3%). In contrast to group I cases, the serous papillary endometrial cancer cases (group III) were characterized by immunonegativity for ER, PR and bcl-2 and high immunoreactivity for p53 (81.8%) and HER-2/neu (45.4%). The endometrioid G3 cases (group II) demonstrated an intermediate immunoprofile, characterized by immunonegativity for ER, PR and HER-2/neu, low immunoreactivity for bcl-2 (7.1%) and high expression of p53 (57.1%). The expression of Ki-67 did not differ significantly comparing the different cases of endometrial cancer. CONCLUSION: This study provides evidence that the immunohistochemical analysis of endometrial carcinoma differentiates between different grades and histological types, thus being useful in the distinction of high risk cases.     

Adenocarcinoma of the endometrium: Analysis of 256 cases with carcinoma limited to the uterine corpus: Pathology review and analysis of prognostic variables

Histologic specimens of all patients undergoing hysterectomy for clinical Stage I adenocarcinoma of the endometrium at Stanford University Hospital between 1959 and 1975 were reexamined. From this group 256 acceptable cases of adenocarcinoma confined to the uterine corpus (Pathologic Stage I) were identified. In patients treated with initial surgery, relapse rate was highly correlated with depth of myometrial invasion (P = 0.0001) and also with the histologic grade of the uterine adenocarcinoma (P = 0.008). Twenty-six patients (10%) had lesions with papillary architecture and anaplastic cytology similar to papillary serous carcinoma of the ovary. These women with uterine papillary serous carcinoma (UPSC) had a 50% relapse rate and accounted for one-half the treatment failures ( ) in the entire study group. Six of the seven upper abdominal relapses in this study were in patients with UPSC, suggesting that this histologic variant may behave more like ovarian serous carcinoma than the usual endometrial adenocarcinoma. Twenty-one patients (9%) had endometrial carcinomas with extensive mucinous differentiation (mucinous carcinoma), while 38% of all the cases of endometrial carcinoma showed at least some focal mucin production. Twenty percent showed focal squamous differentiation. Neither mucinous nor squamous differentiation, as we have applied these designations, were significantly correlated with relapse rate. Among the patients undergoing hysterectomy for clinical Stage I adenocarcinoma, 99 patients were found on review to have lesions which fell short of our current criteria for diagnosis of carcinoma in the uterine corpus and were reinterpreted as metaplasia and/or hyperplasia. None of these patients subsequently developed clinical relapse. The results of this study suggest a need for modification in the FIGO grading system for endometrial cancer and also support a definition of well-differentiated endometrial carcinoma more restrictive than that commonly employed.     

Familial and hormonal risk factors for papillary serous uterine cancer

OBJECTIVES: To identify genetic and non-genetic risk factors for papillary serous uterine cancer. METHODS: A case-control study was conducted. Case women with papillary serous uterine cancer were compared with two control groups: 1) women with endometrioid uterine cancer and 2) healthy women with no past history of cancer. Cases and controls were matched for age (within two years) and ethnic group. All study subjects completed a questionnaire addressing family history. The cases and healthy controls were assessed for factors associated with estrogen exposure. RESULTS: The risks of breast cancer (RR 1.84, CI 1.03-3.31) and of prostate cancer (RR 2.21, CI 0.77-6.37) were higher among the relatives of patients with papillary serous uterine cancer, than among relatives of those with endometrioid uterine cancer. Other significant risk factors included weight at 18 years (p = 0.04) and the use of estrogen replacement therapy (p = 0.04). CONCLUSION: Relatives of women with papillary serous cancer of the uterus had an increased risk of breast and prostate cancer. Hormonal exposure also increases the risk for this cancer. These findings suggest that predisposing genetic factors, possibly related to hormone metabolism, may be common to the three forms of cancer.     

Pathology of the uterine body.

During the past year, evidence has compiled to suggest that uterine carcinosarcomas are, in fact, metaplastic carcinomas and that mitotic counts are of no value in distinguishing between high- and low-grade endometrial stromal sarcomas in stage I cases. The pathologic and biologic behaviour of uterine müllerian adenosarcomas has been comprehensively reviewed. Prognostic factors have been identified in a large series of surgically staged endometrioid adenocarcinomas of the endometrium, while the sinister nature of the serous papillary and clear cell carcinomas of the endometrium have been confirmed. It has been claimed that a papillary pattern of growth is an independent prognostic factor in endometrial neoplasia and shown that the accuracy of macroscopic estimation of depth of myometrial invasion decreases with increasing tumor grade. The value of peritoneal cytologic examination in early stage endometrial adenocarcinoma has been questioned, as has the value of DNA flow cytometry in endometrial neoplasia. The prognostic significance of steroid receptor status has been confirmed and studies of oncogene amplification are beginning to yield prognostically useful information. Evidence is also beginning to emerge concerning chromosomal abnormalities in many women with endometrial adenocarcinoma.     

Synchronous primary cancers of the endometrium and ovary: a case report

Synchronous primary cancers of the endometrium and ovary are found in 5% of women with endometrial cancer and 10% of women with ovarian cancer. In the present case, a multigravid 46-year-old woman complained of lower abdominal pain and abdominal distension. She did not define abnormal uterine bleeding. Screening ultrasound revealed a papillary containing structure, irregular, cystic 16 x 15 x 10 cm right ovarian mass. Preoperative endometrial biopsy revealed endometrioid adenocarcinoma. Ascites sampling, radical hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymphadenectomy, omentectomy, appendectomy and cytologic sampling of the undersurface of the diaphragm were carried out. Intraoperative and histological examinations showed Stage IIIC papillary serous carcinoma and stage IC endometrioid adenocarcinoma. Synchronous genital tract neoplasms constitute a more common clinical problem than would generally be expected.     

Heparanase expression increases throughout the endometrial hyperplasia-cancer sequence.

OBJECTIVE: To assess the expression of heparanase in the different stages leading to endometrial cancer. METHODS: The 38 examined specimens included adenocarcinoma, hyperplasia, and normal endometrium specimens. Heparanase, estrogen, and progesterone receptor expressions were analyzed immunohistochemically and the intensity was scored. RESULTS: Secretory normal endometrium and simple hyperplasia specimens expressed the lowest mean values of expression (1.00 and 0.63, respectively); the complex hyperplasia specimens and G2 endometrioid adenocarcinoma showed the highest values of expression (2.33 and 2.71, respectively). A linear trend (P=0.005) of heparanase expression was observed when comparing the normal endometrium and simple hyperplasia group with the complex hyperplasia+G1 carcinoma group and the G2+G3 carcinoma group. Evaluation of atrophic and inactive endometrium compared with papillary serous carcinomas yielded no significant differences. We found no significant correlation between heparanase expression and estrogen receptor or progesterone receptor expression. CONCLUSION: Heparanase expression was tightly regulated in endometrial tumorigenesis.     

The association between p53 expression, stage and histological features in endometrial cancer

OBJECTIVE: Alterations of the p53 gene have been widely suggested to be relevant to the development of endometrial carcinoma. However, contradictory results have been reported when immunohistochemical determination of p53 expression has been correlated with stage and histological features of the tumours. STUDY DESIGN: Pathology findings were reviewed and p53 immunoperoxidase staining was performed in 240 cases of endometrial carcinoma. RESULTS: Uterine papillary serous adenocarcinomas showed significantly higher p53 overexpression than uterine endometrioid adenocarcinomas (100.0% versus 61.0%, p<0.005). p53 overexpression was significantly higher in the secretory variant (85.7%) than in the typical endometrioid carcinoma (60.0%) (p<0.05). p53 expression did not differ between early (stage I) and advanced (stage II-IV) carcinomas. Likewise, no difference was observed in p53 expression among different architectural grades. The incidence of metastasis to lymph nodes was similar in p53 positive (13.7%) and in p53 negative tumours (12.5%). CONCLUSION: In the present series, p53 immunostaining did not differ between cases with different FIGO stages or histologic characteristics of the tumours. No simple relationship exists between the immunohistochemical determination of p53 expression and the biological aggressiveness of endometrial carcinomas.     

Endometrial histopathology in 700 patients treated with tamoxifen for breast cancer

OBJECTIVE: The aim of this study was the evaluation of endometrial histopathologic findings from 700 patients treated with tamoxifen (Tx) for breast cancer from two medical centers (United States and France). METHODS: A retrospective review of data including histologic slides from 134 hysterectomies and 566 endometrial biopsies from Tx-treated patients who presented with abnormal vaginal bleeding and/or abnormal sonograms was performed. Analysis of histologic characteristics included inactive/atrophic and functional endometria, endometrial polyps, hyperplasia and metaplasia, and endometrial cancer. Duration of Tx therapy was recorded when available, and its correlation with endometrial pathology was assessed. RESULTS: The only statistically significant difference between the data from the United States and France was the number of hysterectomies, which was almost double in France (27% vs 13.7%). Nonpathologic endometria made up 61.14% (inactive/atrophic 46%, functional 15.14%). Pathologic changes were found in 39.86% cases, of which polyps were 23.14%, glandular hyperplasia 8%, and metaplasia 3%; endometrial cancer made up 4.71% (33 cases). Nine cancers were well-differentiated endometrioid adenocarcinomas, and 24 were moderately or poorly differentiated, of which 13 had nonendometrioid components (serous, clear cell, MMMT). Fifteen cancers were found in endometrial polyps; 12 were invasive to the myometrium and 4 to blood vessels. The weight of the uteri exceeded 300 g in 15 cases, with 4 exceeding 900 g. The average age of all patients was 60.91 years and of the cancer patients alone it was 69.26 years. The shortest average duration of Tx therapy (2.5 years) was found in patients with inactive/atrophic endometria and the longest (6.8 years) in patients with endometrial cancer. Patients with endometrial polyps and cancer presented more often with abnormal vaginal bleeding than those with inactive/atrophic endometrium. CONCLUSIONS: Most Tx-treated patients had no pathologic endometrial changes. Endometrial polyps, hyperplasia, and metaplasia, consistent with an estrogen-agonist effect of Tx, were found in roughly one-third of all patients. The endometrial cancers were often high-grade and invasive tumors. Patients with endometrial pathology were more often symptomatic than patients with inactive/atrophic endometria.     

Immunohistochemical characterization of endocervical papillary serous carcinoma

Abstract.   Nofech-Mozes S, Rasty G, Ismiil N, Covens A, Khalifa MA. Immunohistochemical characterization of endocervical papillary serous carcinoma. Int J Gynecol Cancer 2006; 16(Suppl. 1): 286–292.
Endocervical adenocarcinomas are rare and aggressive neoplasms. Papillary serous endocervical adenocarcinomas are the rarest form of endocervical adenocarcinomas. This tumor exhibits morphologic similarities to its counterparts commonly seen in the endometrium, fallopian tubes, ovaries, and peritoneum, which are known to have an aggressive behavior. Because of the rarity of this tumor, little is known about its immunophenotyping. In this study, we included ten cases of papillary serous carcinomas arising from the uterine cervix (PSCC) diagnosed in the absence of a primary endometrial malignancy. We studied their immunohistochemical profile, using a panel of antibodies against Ki67, bcl-2, p53, carcinoembryonic antigen (CEA), and CD10, and compared them to 20 consecutive cases of cervical adenocarcinoma of conventional cell subtypes (CAC) (15 mucinous, 3 adenosquamous, and 2 endometrioid). Immunostaining was recorded semiquantitatively. Patients with PSCC ranged in age from 27 to 79 years (mean = 51.6 ± 19.1), while the conventional cell subtypes control group were 28–90 years old (mean = 47.5 ± 16.9). Only p53 and CEA immunostaining significantly correlated with the PSCC morphology ( P = 0.001 and P = 0.016, respectively) as shown by Cochran–Mantel–Haenszel Statistics (Modified Ridit Scores). PSCC is a distinctive immunophenotypic subtype of endocervical adenocarcinoma with significantly higher p53 and lower CEA reactivity than other more common histologic subtypes.     

Papillary Serous Carcinoma of the Uterus: Increased Risk of Subsequent or Concurrent Development of Breast Carcinoma

OBJECTIVE: Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. METHODS: The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and chi(2) tests. RESULTS: Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC (P < 0.001). CONCLUSION: Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus.     

Synchronous carcinomas of endometrium and ovary

Five cases of synchronous carcinomas of uterine endometrium and ovary are reported. All uterine cancers were typical endometrial adenocarcinomas. Among the ovarian cancers, four were serous papillary cystadenocarcinomas and one was an endometrioid carcinoma. There is much controversy with respect to staging and management of such cases since these tumors may represent either two synchronously occurring primaries or a single primary with metastases. It is suggested that when each tumor is confined within the limits of its tissue of origin the tumors may be considered as two separate primaries and surgery may be less aggressive. When there is evidence that at least one tumor is spreading to adjacent tissues and organs the question of two separate primaries or one metastatic tumor becomes academic only and aggressive surgical treatment with adjuvant chemotherapy is indicated.     

Synchronous carcinomas of endometrium and ovary

Five cases of synchronous carcinomas of uterine endometrium and ovary are reported. All uterine cancers were typical endometrial adenocarcinomas. Among the ovarian cancers, four were serous papillary cystadenocarcinomas and one was an endometrioid carcinoma. There is much controversy with respect to staging and management of such cases since these tumors may represent either two synchronously occurring primaries or a single primary with metastases. It is suggested that when each tumor is confined within the limits of its tissue of origin the tumors may be considered as two separate primaries and surgery may be less aggressive. When there is evidence that at least one tumor is spreading to adjacent tissues and organs the question of two separate primaries or one metastatic tumor becomes academic only and aggressive surgical treatment with adjuvant chemotherapy is indicated.     

WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary, and endometrium.

The Wilms' tumor gene WT1 plays complex roles in the development of the organs of the genitourinary tract and mesothelium, as well as Wilms' tumors. Although its biologic role is still unclear, most serous carcinomas of the ovary and peritoneum, mesotheliomas, and Wilms' tumor have been shown to express WT1. A recent study, however, found no WT1 expression in serous carcinomas of the endometrium, suggesting that WT1 could be useful in identifying the primary site of serous carcinomas. We examined the expression of WT1 and p53 by immunohistochemistry in 69 cases of endometrial carcinoma (35 endometrioid, 18 clear cell, 16 serous), 68 cases of ovarian carcinoma (28 serous, 11 endometrioid, 18 clear cell, and 11 mucinous), 14 fallopian tube carcinomas (12 serous, 2 endometrioid), and 20 primary peritoneal serous carcinomas. WT1 nuclear reactivity of any extent and intensity was considered positive. Immunohistochemical stains were evaluated semiquantitatively using a four-tiered scale. Among endometrial carcinomas, WT1 immunoreactivity was seen in 10 of 16 serous, but in none of 35 endometrioid or 18 clear cell carcinomas. Among ovarian tumors, WT1 expression was seen in 24 of 28 serous and 4 of 18 clear cell carcinomas, but in none of 11 endometrioid and 11 mucinous tumors. All 12 serous carcinomas but none of 2 endometrioid carcinomas of the fallopian tube were positive for WT1. WT1 expression was seen in 19 of 20 serous primary peritoneal carcinomas. The difference in WT1 expression was highly significant between serous and other types of tumors in all sites (p<0.0001, chi-square test), although the level of WT1 expression was significantly different among serous carcinomas arising at different sites (p<0.0001, Kruskal-Wallis test). A significant positive correlation was found between the level of p53 and WT1 expression in all carcinomas combined (r = 0.3935, p<0.0001, Spearman test), but when only serous carcinomas were analyzed, the correlation between p53 and WT1 expression levels did not reach statistical significance. Our results suggest that WT1 expression in epithelial tumors of the female genital tract may be related to cell differentiation and histologic subtypes of carcinomas, rather than to primary site of origin.     

Advances in the management of endometrial adenocarcinoma. A review

Endometrial adenocarcinoma is the most common and curable gynecologic neoplasm; the five-year survival for women with surgical stage I disease ranges from 83% to 93%; stage II, 73%; stage III, 52%; and stage IV, 27%. The absence of an asymptomatic latency phase amenable to detection through screening and the already excellent cure rates seen with early-stage disease have precluded the need for endometrial cancer screening programs. Adenocarcinomas constitute 97% of endometrial cancers, with endometrioid the most common histologic subtype. Two different pathways of endometrial carcinogenesis exist. One arises in a background of estrogen excess, giving rise to atypical hyperplasia as the malignant precursor of the more common endometrioid adenocarcinomas. The use of oral contraceptives has consistently been shown to decrease the risk of developing endometrial carcinoma via this pathway, with 12 months or more of continuous use decreasing the lifetime risk by 40-50%. The alternate pathway of endometrial carcinogenesis represents malignant transformation of atrophic endometrium and proceeds through endometrial intraepithelial carcinoma as the malignant precursor of the more virulent serous papillary and clear cell endometrial adenocarcinomas. The staging of endometrial cancer (according to the International Federation of Obstetrics and Gynecology) is surgical. Recent studies suggest a therapeutic benefit associated with extensive retroperitoneal lymph node evaluation to determine the disease extent and thereby more effectively direct potentially life-saving adjuvant therapy. Adjuvant radiation therapy, known to have survival benefit in advanced-stage disease, may also have survival benefit in intermediate-risk surgical stage I disease on the basis of results recently released from a Gynecologic Oncology Group study. The use of radiation therapy, systemic chemotherapy and hormonal therapy, alone or in combination, is recommended for primary advanced and recurrent disease.